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While ER\u2010T improves patient adherence, clinical studies have not demonstrated superior outcomes compared to IR\u2010T. However, the underlying reasons for this discrepancy remain unclear. This study aimed to evaluate tacrolimus exposure under non\u2010adherent dosing behaviors with IR\u2010T and ER\u2010T and to provide insights for selecting the optimal tacrolimus formulation. Monte Carlo simulations were conducted to assess the proportion of target attainment (%PTA) and deviation time (DT) from the therapeutic range in scenarios involving delayed or missed doses, based on published population pharmacokinetic models. The influence of renal function, the post\u2010transplantation period, and hematocrit levels on %PTA and DT were also analyzed. Our findings revealed that patients on ER\u2010T exhibited lower %PTA and longer DT than those on IR\u2010T when doses were delayed or missed, reflecting poorer \u201cforgiveness.\u201d This observation elucidates the lack of clinical superiority observed for ER\u2010T in previous studies. Furthermore, fast metabolizers experienced worse forgiveness with ER\u2010T, exacerbating the challenge of maintaining therapeutic levels. Additionally, a web\u2010based dashboard was developed to calculate the %PTA and DT for individual patients and to provide formulation recommendations tailored to their dosing behaviors and clinical characteristics. In conclusion, adherence and forgiveness play a crucial role in the success of pharmacotherapy. This study highlights the significance of pharmacokinetic modeling and simulation in providing evidence\u2010based recommendations for selecting the optimal tacrolimus formulation.<\/jats:p>","DOI":"10.1002\/jcph.70021","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T08:34:36Z","timestamp":1743064476000},"page":"980-987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Once\u2010 Versus Twice\u2010Daily Tacrolimus Therapy: Does Improved Adherence Lead to Better Efficacy?\u2014A Pharmacokinetic Perspective"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0229-8263","authenticated-orcid":false,"given":"Zi\u2010yan","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Pharmacy Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"School of Pharmacy Shanghai Jiao Tong University  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